Efficient modification of peroxydisulfate oxidation reactions of nitrogen-containing heterocycles 6-methyluracil and pyridine

• Alfiya R. Gimadieva,
• Yuliya Z. Khazimullina,
• Aigiza A. Gilimkhanova and
• Akhat G. Mustafin

Beilstein J. Org. Chem. 2024, 20, 2599–2607, doi:10.3762/bjoc.20.219

• Alfiya R. Gimadieva Yuliya Z. Khazimullina Aigiza A. Gilimkhanova Akhat G. Mustafin Ufa Institute of Chemistry at Ufa Federal Research Center, Russian Academy of Sciences, 71 prosp. Oktyabrya, 450054 Ufa, Russian Federation 10.3762/bjoc.20.219 Abstract Nitrogen-containing heterocyclic compounds

• convenience of the process, our objective is to enhance the efficiency of the Elbs and Boyland–Sims peroxydisulfate oxidation reactions. Results and Discussion We conducted research to enhance the product yield of peroxydisulfate oxidation reactions of specific nitrogen-containing heterocyclic compounds, such

• overoxidized and leads to destruction of the heterocyclic ring. As a result, the yield of the final products decreases. Furthermore, oxidation is incomplete at temperatures lower than the optimal temperature. The oxidation of MU (1), TMU (4), and pyridine (7) using ammonium peroxydisulfate (APS) was conducted

Synthesis and cytotoxicity studies of novel N-arylbenzo[h]quinazolin-2-amines

• Battini Veeraiah,
• Kishore Ramineni,
• Dabbugoddu Brahmaiah,
• Nangunoori Sampath Kumar,
• Hélène Solhi,
• Rémy Le Guevel,
• Chada Raji Reddy,
• Frédéric Justaud and
• René Grée

Beilstein J. Org. Chem. 2024, 20, 2592–2598, doi:10.3762/bjoc.20.218

• attractive results in this area. Keywords: Buchwald–Hartwig coupling; cytotoxicity; heterocycles; Pd catalysis; quinazolines; Introduction Nitrogen-containing heterocyclic molecules are ubiquitous in living systems. Among them, quinazolines, and especially the 4-aminoquinazolines (type A molecules, Figure

• ) exhibited a relatively broad cytotoxicity on four cancer cell lines among the seven assayed. On the other hand, two others (4f and 4h) were active only on Caco-2, while another one (4d) only on HCT-116. Thus, the results obtained with these compounds indicate that such a novel heterocyclic scaffold, which

Base-promoted cascade recyclization of allomaltol derivatives containing an amide fragment into substituted 3-(1-hydroxyethylidene)tetronic acids

• Andrey N. Komogortsev,
• Constantine V. Milyutin and
• Boris V. Lichitsky

Beilstein J. Org. Chem. 2024, 20, 2585–2591, doi:10.3762/bjoc.20.217

• ; 1,1′-carbonyldiimidazole; 3-hydroxypyran-4-ones; tetronic acid; Introduction 3-Hydroxypyran-4-one derivatives are an important class of heterocyclic compounds widely represented in various naturally occurring sources [1][2][3][4]. Products of this type demonstrate a broad range of biological activity

• unit and a nucleophilic fragment in the side chain various transformations are possible. For example, a pyranone ring can be opened and recyclized into the novel heterocyclic system. Indeed, previously we have shown that various allomaltols 1 containing a hydrazide moiety are converted into substituted

Photoredox-catalyzed intramolecular nucleophilic amidation of alkenes with β-lactams

• Valentina Giraldi,
• Giandomenico Magagnano,
• Daria Giacomini,
• Pier Giorgio Cozzi and
• Andrea Gualandi

Beilstein J. Org. Chem. 2024, 20, 2461–2468, doi:10.3762/bjoc.20.210

• -centered radicals, such as aminyl, amidyl, or iminyl radicals, N-heterocyclic amidyl radicals were largely underinvestigated despite their importance as intermediates or relevant N-heterocyclic products in medicinal chemistry [7][8][9][10]. Recently, photoredox catalysis has emerged as a novel area of

• ]. Through tailored molecular design, it is possible to enhance the oxidation capability of these catalysts, enabling the utilization of less reactive alkenes and even aromatic molecules such as toluene [32]. Until now, heterocyclic amides such as β-lactam compounds have not been employed in alkene

Evaluating the halogen bonding strength of a iodoloisoxazolium(III) salt

• Dominik L. Reinhard,
• Anna Schmidt,
• Marc Sons,
• Julian Wolf,
• Elric Engelage and
• Stefan M. Huber

Beilstein J. Org. Chem. 2024, 20, 2401–2407, doi:10.3762/bjoc.20.204

• that six-membered core structures are also weaker XB donors (iodininium 3OTf) than iodolium 1OTf [13]. Furthermore, the importance of substituents in the core and on the outer rings was demonstrated (XB donors 2OTf and 4OTf). Nachtsheim reported the synthesis of N-heterocyclic substituted monocationic

• donors [16][17] from our group as well as of dicationic N-heterocyclic-substituted monodentate catalysts by Nachtsheim [15]. While such compounds are necessary to activate neutral substrates in more challenging reactions, monodentate and monocationic congeners provide sufficient activation in halide

Synthesis, electrochemical properties, and antioxidant activity of sterically hindered catechols with 1,3,4-oxadiazole, 1,2,4-triazole, thiazole or pyridine fragments

• Daria A. Burmistrova,
• Andrey Galustyan,
• Nadezhda P. Pomortseva,
• Kristina D. Pashaeva,
• Maxim V. Arsenyev,
• Oleg P. Demidov,
• Mikhail A. Kiskin,
• Andrey I. Poddel’sky,
• Nadezhda T. Berberova and
• Ivan V. Smolyaninov

Beilstein J. Org. Chem. 2024, 20, 2378–2391, doi:10.3762/bjoc.20.202

• , Leninskii prosp., 31, 119991, Moscow, Russia Institute of Inorganic Chemistry, University of Tübingen, Auf der Morgenstelle 18, 72076, Tübingen, Germany 10.3762/bjoc.20.202 Abstract A series of new RS−, RS−CH2− and R2N−CH2-functionalized сatechols with heterocyclic fragments such as 1,3,4-oxadiazole, 1,2,4

• -triazole, thiazole, or pyridine were synthesized by the reaction of 3,5-di-tert-butyl-o-benzoquinone or 3,5-di-tert-butyl-6-methoxymethylcatechol with different heterocyclic thiols. The S-functionalized catechols were prepared by the Michael reaction from 3,5-di-tert-butyl-o-benzoquinone and the

• established for these compounds. The electrochemical behavior of the studied compounds is influenced by several factors: the nature of the heterocycle and its substituents, the presence of a sulfur atom in the catechol ring, or a thione group in the heterocyclic core. The radical scavenging activity and

Asymmetric organocatalytic synthesis of chiral homoallylic amines

• Nikolay S. Kondratyev and
• Andrei V. Malkov

Beilstein J. Org. Chem. 2024, 20, 2349–2377, doi:10.3762/bjoc.20.201

• tool for the rapid construction of medicinal chemistry-relevant heterocyclic homoallylic amines in an enantioselective manner without involving nucleophilic allylation. The highly functionalised products offer the possibility of further derivatisation. Other catalytic approaches In 2017, the

Tandem diazotization/cyclization approach for the synthesis of a fused 1,2,3-triazinone-furazan/furoxan heterocyclic system

• Yuri A. Sidunets,
• Valeriya G. Melekhina and
• Leonid L. Fershtat

Beilstein J. Org. Chem. 2024, 20, 2342–2348, doi:10.3762/bjoc.20.200

• Federation 10.3762/bjoc.20.200 Abstract A straightforward protocol for the synthesis of a previously unknown [1,2,5]oxadiazolo[3,4-d][1,2,3]triazin-7(6H)-one heterocyclic system was developed. The described approach is based on tandem diazotization/azo coupling reactions of (1,2,5-oxadiazolyl)carboxamide

• derivatives bearing both aromatic and aliphatic substituents. The NO-donor ability of the synthesized furoxano[3,4-d][1,2,3]triazin-7(6H)-ones was additionally evaluated. The elaborated method provides access to novel nitrogen heterocyclic compounds with potential applications as drug candidates or

• , anticancer, non-steroidal anti-inflammatory, antihypertensive, antipsychotic, anxiolytic and in other pharmaceuticals [3][4][5]. Therefore, considering the diversity of biological properties, development of reliable approaches for the synthesis of new nitrogen heterocyclic systems is a highly urgent goal

Hydrogen-bond activation enables aziridination of unactivated olefins with simple iminoiodinanes

• Phong Thai,
• Lauv Patel,
• Diyasha Manna and
• David C. Powers

Beilstein J. Org. Chem. 2024, 20, 2305–2312, doi:10.3762/bjoc.20.197

• -trifluoromethylsulfonyl)aziridine 6c was furnished in 47% yield. Similarly, 2,6-difluorosulfonyl-substituted iminoiodinane 2d afforded aziridine 6d in 52% yield. The aziridination procedure was tolerant of heterocyclic substituents on the iminoiodinane, N-(5-methylpyridin-2-ylsulfonyl)aziridine 6e could be obtained in 46

Deuterated reagents in multicomponent reactions to afford deuterium-labeled products

• Kevin Schofield,
• Shayna Maddern,
• Yueteng Zhang,
• Grace E. Mastin,
• Rachel Knight,
• Wei Wang,
• James Galligan and
• Christopher Hulme

Beilstein J. Org. Chem. 2024, 20, 2270–2279, doi:10.3762/bjoc.20.195

• (Scheme 8) [47]. The Groebke–Blackburn–Bienaymé (GBB) reaction is an intramolecular variant of the Ugi reaction where the intermediate nitrilium ion is intercepted by heteroatoms from the amino-heterocyclic input. Discovered in 1998, and reported independently by three different research groups, it is a

Heterocycle-guided synthesis of m-hetarylanilines via three-component benzannulation

• Andrey R. Galeev,
• Maksim V. Dmitriev,
• Alexander S. Novikov and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2024, 20, 2208–2216, doi:10.3762/bjoc.20.188

• -diketones has been developed. The electron-withdrawing power of the heterocyclic substituent (which can be estimated on the basis of calculated Hammett constants) in the 1,3-diketone plays a pivotal role in the studied reaction. The series of meta-hetarylanilines prepared (21–85% isolated yield

• was released [57] allowing direct comparison of different substituents. On the basis of the calculated Hammett constants, we have selected a model series of 1,3-diketones, bearing heterocyclic substituents with a range of electron-withdrawing ability (Figure 2). For the amine model series, we used

• reaction in the presence of molecular sieves and 1.5-fold excess of aniline (conditions B) dramatically reduced the reaction time to 1 d, allowing isolation of diarylamine 3ac in 75% yield (Scheme 2). Next, we started to screen various heterocyclic 1,3-diketones with the model amine series. The reaction of

O,S,Se-containing Biginelli products based on cyclic β-ketosulfone and their postfunctionalization

• Kateryna V. Dil and
• Vitalii A. Palchykov

Beilstein J. Org. Chem. 2024, 20, 2143–2151, doi:10.3762/bjoc.20.184

• synthesis of new S-heterocyclic systems we tried to combine the broad synthetic potential of Biginelli condensation and high reactivity β-ketosulfone 1 (dihydro-2H-thiopyran-3(4H)-one-1,1-dioxide) in various condensation reactions [14][15][16][17][18][19][20]. It was also worth mentioning that the thiopyran

• , Leishmania amazonensis, Tcruzi epimastigota, Dengue larvicida, and for selected cases Alzheimer and Sars-COVID. For more details, see Table S1 (Supporting Information File 1). Conclusion In summary, we have demonstrated the catalytic regioselective Biginelli synthesis of new S-heterocyclic systems ‒ 4-aryl

Efficacy of radical reactions of isocyanides with heteroatom radicals in organic synthesis

• Akiya Ogawa and
• Yuki Yamamoto

Beilstein J. Org. Chem. 2024, 20, 2114–2128, doi:10.3762/bjoc.20.182

• phenanthridines via silver-catalyzed radical sulfonylation–cyclization of 2-isocyanobiphenyls (Scheme 25) [98]. Wang et al. reported a radical borylative cyclization of 2-isocyanobiaryls with N-heterocyclic carbene borane (Scheme 26) [99]. The boryl radical generated via hydrogen abstraction in the presence of di

Multicomponent syntheses of pyrazoles via (3 + 2)-cyclocondensation and (3 + 2)-cycloaddition key steps

• Ignaz Betcke,
• Alissa C. Götzinger,
• Maryna M. Kornet and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2024, 20, 2024–2077, doi:10.3762/bjoc.20.178

Harnessing the versatility of hydrazones through electrosynthetic oxidative transformations

• Aurélie Claraz

Beilstein J. Org. Chem. 2024, 20, 1988–2004, doi:10.3762/bjoc.20.175

• solution, as described in the experimental section. This information is provided in brackets. Review Synthesis of azacycles Nitrogen-containing heterocyclic compounds possess numerous applications in various domains such as materials science, agrochemistry and medicinal chemistry. Especially, 60% of all

• electrochemical approach constitutes an advantageous alternative to previous methods, which required the preparation of difficult-to-handle hydrazonoyl halides for the synthesis of 1-aryl-5-amino-1,2,4-triazoles from cyanamide [56][57]. Pyrazolines are highly important heterocyclic motifs in pharmaceutical and

Regioselective alkylation of a versatile indazole: Electrophile scope and mechanistic insights from density functional theory calculations

• Pengcheng Lu,
• Luis Juarez,
• Paul A. Wiget,
• Weihe Zhang,
• Krishnan Raman and
• Pravin L. Kotian

Beilstein J. Org. Chem. 2024, 20, 1940–1954, doi:10.3762/bjoc.20.170

• heterocycles with interesting biological and medicinal properties. Indazole, also called benzpyrazole, is a heterocyclic organic compound commonly found as a structural motif in natural products, pharmaceuticals, agrochemicals, and bioactive compounds [1][2][3][4][5][6]. Indazole-containing compounds possess a

Solvent-dependent chemoselective synthesis of different isoquinolinones mediated by the hypervalent iodine(III) reagent PISA

• Ze-Nan Hu,
• Yan-Hui Wang,
• Jia-Bing Wu,
• Ze Chen,
• Dou Hong and
• Chi Zhang

Beilstein J. Org. Chem. 2024, 20, 1914–1921, doi:10.3762/bjoc.20.167

• is an important heterocyclic framework in natural products and biologically active molecules, and the efficient synthesis of this structural motif has received much attention in recent years. Herein, we report a (phenyliodonio)sulfamate (PISA)-mediated, solvent-dependent synthesis of different

• ); isoquinolinone; solvent-dependence; Introduction Isoquinolinone is an important heterocyclic structure found in many natural products and biologically active compounds, including pharmaceuticals [1]. For instance, lycoricidine, found in the medicinal plant Lycoris radiata, may inhibit the MCPyV LT protein

• –intramolecular cyclization cascade with excellent chemoselectivity in aqueous CH3CN [25]. Herein, as part of our continuing studies of heterocyclic scaffold synthesis mediated by hypervalent iodine reagents, we present the solvent-dependent chemoselective synthesis of a series of isoquinolinones mediated by PISA

Novel oxidative routes to N-arylpyridoindazolium salts

• Oleg A. Levitskiy,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2024, 20, 1906–1913, doi:10.3762/bjoc.20.166

• containing electron-donating and electron-withdrawing groups were taken as the starting compounds (Scheme 2). As an oxidant, bis(trifluoroacetoxy)iodobenzene (PIFA) was used. It allowed obtaining the targeted heterocyclic cations in practical 49–54% yield for all starting diarylamines. Notably, a minor

• diaryldihydrophenazine was increased (10%). Thus, protonation completely suppressed the intramolecular cyclization route. Heterocyclic salts S1–S3 were obtained as amorphous solids, soluble in polar solvents (acetonitrile, DMF, acetone) and chlorinated hydrocarbons (CHCl3, CH2Cl2). The structure of new N

Access to 2-oxoazetidine-3-carboxylic acid derivatives via thermal microwave-assisted Wolff rearrangement of 3-diazotetramic acids in the presence of nucleophiles

• Ivan Lyutin,
• Vasilisa Krivovicheva,
• Grigory Kantin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2024, 20, 1894–1899, doi:10.3762/bjoc.20.164

• organic synthesis as a route to generate ketenes is being actively investigated, involving both acyclic and carbocyclic diazocarbonyl compounds [26]. At the same time, the use of diazoheterocyclic reagents (including diazotetramic acids) in this transformation, with the formation of heterocyclic ring

2-Heteroarylethylamines in medicinal chemistry: a review of 2-phenethylamine satellite chemical space

• Carlos Nieto,
• Alejandro Manchado,
• Ángel García-González,
• David Díez and
• Narciso M. Garrido

Beilstein J. Org. Chem. 2024, 20, 1880–1893, doi:10.3762/bjoc.20.163

• structural hopping strategy, as five- or six-membered heterocyclic aromatic rings are widespread entities in drug discovery [4]. In this sense, any bioactive molecule enclosing a benzene ring in its initial optimization stages could undergo a heteroaromatic replacement. 2-Phenethylamines are notable

The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)

• Cristina Martini,
• Muhammad Idham Darussalam Mardjan and
• Andrea Basso

Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162

• already discussed in section 1.3, Brunschweiger et al. [47] reported the synthesis of DNA–imidazole heterocyclic conjugates by the GBB-3CR. An alternative to the previously discussed encapsulated solution-phase synthesis is the solid-phase approach in which the DNA barcodes are synthesized on CPG

• acid were essential for the success of the reaction (Scheme 16). A cheminformatic analysis revealed that GBB-based encoded libraries could cover a diverse chemical space, different from the one covered by encoded libraries obtained with other isocyanide-based MCRs. 2.2 Novel heterocyclic amidines

• -pot two-step procedure, combining the GBB-3CR and an acid-assisted deprotection reaction, to get a library of imidazo[2,1-f][1,2,4]triazin-4(3H)-ones 46, characterized by a flat heterocyclic ring system displaying the essential triad. Guanine derivatives are typically synthesized through a sequential

A facile three-component route to powerful 5-aryldeazaalloxazine photocatalysts

• Ivana Weisheitelová,
• Radek Cibulka,
• Marek Sikorski and
• Tetiana Pavlovska

Beilstein J. Org. Chem. 2024, 20, 1831–1838, doi:10.3762/bjoc.20.161

• purification. Thus, it significantly improves existing approaches. Keywords: catalysis; deazaalloxazine; flavin; multicomponent approach; one-pot reaction; Introduction Heterocyclic compounds containing pyrimidine and quinoline motifs in their structure, both of natural and synthetic origin, find a wide set

• mechanism, see Supporting Information File 1). Such results with previous reports on DMSO acting as a methine source in the synthesis of heterocyclic compounds [35][36] are opening a new avenue for the green synthesis of non-substituted 5-deazaalloxazines in a pseudo MCR fashion. Conclusion In summary, we

Hetero-polycyclic aromatic systems: A data-driven investigation of structure–property relationships

• Sabyasachi Chakraborty,
• Eduardo Mayo Yanes and
• Renana Gershoni-Poranne

Beilstein J. Org. Chem. 2024, 20, 1817–1830, doi:10.3762/bjoc.20.160

• -driven investigation of the newly generated COMPAS-2 dataset, which contains ~500k molecules consisting of 11 types of aromatic and antiaromatic rings and ranging in size from one to ten rings. Our analysis explores the effects of electron count, geometry, atomic composition, and heterocyclic composition

• new insights into these molecules. [Note: cata-condensed refers to fused PASs in which each atom participates in no more than two rings]. The second installment, COMPAS-2 [9], houses ~500k cata-condensed heterocyclic-PASs (cc-hPASs) comprising 11 types of aromatic and antiaromatic rings containing the

• [9] and COMPAS-1 [6]. The second, third, and fourth sections then present analyses of the data, each focused on different structural aspects: global electronic and geometric features, atomic composition, and heterocyclic composition. A roadmap of the article structure is shown in Figure 2. Comparison

Ugi bisamides based on pyrrolyl-β-chlorovinylaldehyde and their unusual transformations

• Alexander V. Tsygankov,
• Vladyslav O. Vereshchak,
• Tetiana O. Savluk,
• Serhiy M. Desenko,
• Valeriia V. Ananieva,
• Oleksandr V. Buravov,
• Yana I. Sakhno,
• Svitlana V. Shishkina and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2024, 20, 1773–1784, doi:10.3762/bjoc.20.156

• bisamides based on the same aldehydes and amines may also demonstrate biological activity. In view of these facts, we decided to develop a new approach for the synthesis of hybrid molecules containing substituted heterocyclic and peptidomimetic moieties. The first stage of this approach was the preparation

• Ukraine "Directed synthesis, chemical transformations and properties of new nitrogen-containing heterocyclic compounds" (0122U001857).

Syntheses and medicinal chemistry of spiro heterocyclic steroids

• Laura L. Romero-Hernández,
• Ana Isabel Ahuja-Casarín,
• Penélope Merino-Montiel,
• Sara Montiel-Smith,
• José Luis Vega-Báez and
• Jesús Sandoval-Ramírez

Beilstein J. Org. Chem. 2024, 20, 1713–1745, doi:10.3762/bjoc.20.152

• is compelling evidence that incorporating a heterocyclic moiety into a steroid can alter its pharmacological and pharmacokinetic properties, driving intense interest in the synthesis of such hybrids among research groups. In this review, we present an overview of recent synthetic methodologies

• , spanning the period from 2000 to 2023, for the preparation of spiro heterocyclic steroids. The compounds surveyed encompass four-, five-, six-, and seven-membered heterocycles appended to various positions of steroidal backbones, with spirocycles containing oxygen, nitrogen, and sulfur atoms being

• heterocyclic moieties containing three or more (hetero)cycles. Moreover, many compounds are accompanied by data on their biological activities, such as antiproliferative, antimalarial, antimicrobial, antifungal, steroid antagonist, and enzyme inhibition, among others, aimed at furnishing pertinent insights for